The lining of blood vessels, called the endothelium, is capable of releasing substances which allow blood vessels to relax in response to a variety of stimuli. One factor released is known as endothelium-derived relaxant factor (EDRF). Acetylcholine is capable of promoting release of EDRF from blood vessels and we have previously shown that in patients with hypertension, there is an endothelial-dependent abnormality in the forearm microvasculature. This study was designed to investigate if such an endothelial abnormality also exists in the coronary arteries of patients with hypertension. We studied 13 patients with hypertension and normal epicardial coronary arteries who were undergoing cardiac catheterization for chest pain. Some of these patients had a reduced vasodilator response to rapid atrial pacing. The same patients also had reduced response to intracoronary administration of acetylcholine. However, when an endothelial independent vasodilator, nitroprusside, was administered, these patients had a normal response. Thus, chest pain in patients with hypertension and reduced vasodilator reserve may be associated with an endothelial abnormality of the small vessels of the heart. However, this finding is not uniformly present in the coronary microvasculature of all patients with hypertension.